Allogeneic bone marrow or peripheral blood stem cell transplantation traditionally uses myeloablative regimen for conditioning to enable grafting of donor's stem cells. Animal experiments have shown that a milder non-myeloablative conditioning regimen does allow engraftment to occur. Nonmyeloablative conditioning regimens are low-intensity immunosuppressive treatment given to the recipient before infusion of donor's stem cells. It was reported to have decreased immediate procedural mortality, in particular those secondary to acute graft versus host reaction. However, it did give rise to higher risks of graft rejection, tumour tolerance and disease progression. Fortunately, appropriately administered donor lymphocyte infusion has been shown to establish full donor chimerism (complete donor stem cell grafting in the recipient's bone marrow) and potentiate antitumour effect (graft versus tumour reaction). The reduction of immediate transplant mortality allows the procedure to be carried out in older age groups, patients with concomitant diseases that otherwise would have made the patients unfit for the procedure, patients with non-malignant disorders such as congenital immune deficiencies, autoimmune disorders or thalassaemia majors. The regimen also allows transplantation of genetically manipulated haemopoietic stem cells (gene thrapy) to be carried out more readily in the immediate future. Lastly, the regimen may serve as a platform for immunotherapy using specific T cell clones for anti-tumour therapy with or without the knowledge of known tumour antigen.
seconds ; regimen ; Conditioning (Psychology) ; Stem Cells ; Exertional dyspnea

Two duplex PCR assays were established for the detection of C. trachomatis (Ct), N. gonorrhoeae (GC), M. hominis (Mh), and U. urealyticum (Uu). These assays were used on clinical specimens obtained from women with Premature Rupture of Membrane or Post Partum Fever, from preterm infants, as well as from women with uneventful pregnancies and their babies delivered vaginally at term. The analytical sensitivity of the duplex PCR assays with internal controls incorporated is 7.0, 19.0, 5x10(3) and 7x10(2) genome copies per reaction for Ct, GC, Mh and Uu respectively. Specificity was demonstrated by the amplification of only target DNA in the presence of other organisms. Among 40 women with normal, at term, deliveries, there were 6 positives for Ct, 2 for GC and 1 for Uu. None of these women had signs of genital tract infection. The Mh/Uu PCR was positive in 11 of 40 PROM cases, with 7 women positive for Uu, 2 for Mh and 2 others for both organisms. Of 40 blood cultures taken from post-partum maternal infections, 6 were positive for Ct and 1 for Mh. Respiratory secretions from 30 premature neonates yielded 5 positives for Uu and one each for Mh and Ct. In contrast, there was only 1 positive result (for Mh) in 30 mature neonates. With 1 exception, all mycoplasma and ureaplasma positives were confirmed by culture and the concordance between paired tracheal aspirates and nasopharyngeal swabs from neonates was 96.7%. These results show the potential use of the duplex PCR assays for the diagnosis of maternal and neonatal disease caused by the four urogenital pathogens.
Polymerase Chain Reaction ; Human Females ; seconds ; Neisseria gonorrhoeae ; Infant, Newborn

Aspirin exacerbated respiratory disease (AERD) is a clinical syndrome characterized by chronic rhinosinusitis with nasal polyposis and aspirin hypersensitivity. The aspirin-induced bronchospasm is mediated by mast cell and eosinophilic inflammation. Recently, it has been reported that the expression of discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2) is up-regulated in lung cancers and is regulated by transcription factor AP-2 alpha (TFAP2A), a component of activator protein-2 (AP-2) that is known to regulate IL-8 production in human lung fibroblasts and epithelial cells. To investigate the associations between AERD and DCBLD2 polymorphisms, 12 common variants were genotyped in 163 AERD subjects and 429 aspirin tolerant asthma (ATA) controls. Among these variants, seven SNPs (rs1371687, rs7615856, rs828621, rs828618, rs828616, rs1062196, and rs8833) and one haplotype (DCBLD2-ht1) show associations with susceptibility to AERD. In further analysis, this study reveals significant associations between the SNPs or haplotypes and the percentage of forced expiratory volume in one second (FEV1) decline following aspirin challenge using multiple linear regression analysis. Furthermore, a non-synonymous SNP rs16840208 (Asp723Asn) shows a strong association with FEV1 decline in AERD patients. Although further studies for the non-synonymous Asp723Asn variation are needed, our findings suggest that DCBLD2 could be related to FEV1-related phenotypes in asthmatics.
Adolescent ; Adult ; Aged ; Alleles ; Asian Continental Ancestry Group/*genetics ; Aspirin/*adverse effects ; Asthma, Aspirin-Induced/etiology/*genetics ; Female ; Forced Expiratory Volume/drug effects/genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Humans ; Male ; Membrane Proteins/*genetics ; Middle Aged ; *Polymorphism, Single Nucleotide ; Regression Analysis ; Republic of Korea ; Risk Factors ; Young Adult

Aspirin exacerbated respiratory disease (AERD) is a clinical syndrome characterized by chronic rhinosinusitis with nasal polyposis and aspirin hypersensitivity. The aspirin-induced bronchospasm is mediated by mast cell and eosinophilic inflammation. Recently, it has been reported that the expression of discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2) is up-regulated in lung cancers and is regulated by transcription factor AP-2 alpha (TFAP2A), a component of activator protein-2 (AP-2) that is known to regulate IL-8 production in human lung fibroblasts and epithelial cells. To investigate the associations between AERD and DCBLD2 polymorphisms, 12 common variants were genotyped in 163 AERD subjects and 429 aspirin tolerant asthma (ATA) controls. Among these variants, seven SNPs (rs1371687, rs7615856, rs828621, rs828618, rs828616, rs1062196, and rs8833) and one haplotype (DCBLD2-ht1) show associations with susceptibility to AERD. In further analysis, this study reveals significant associations between the SNPs or haplotypes and the percentage of forced expiratory volume in one second (FEV1) decline following aspirin challenge using multiple linear regression analysis. Furthermore, a non-synonymous SNP rs16840208 (Asp723Asn) shows a strong association with FEV1 decline in AERD patients. Although further studies for the non-synonymous Asp723Asn variation are needed, our findings suggest that DCBLD2 could be related to FEV1-related phenotypes in asthmatics.
Adolescent ; Adult ; Aged ; Alleles ; Asian Continental Ancestry Group/*genetics ; Aspirin/*adverse effects ; Asthma, Aspirin-Induced/etiology/*genetics ; Female ; Forced Expiratory Volume/drug effects/genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Humans ; Male ; Membrane Proteins/*genetics ; Middle Aged ; *Polymorphism, Single Nucleotide ; Regression Analysis ; Republic of Korea ; Risk Factors ; Young Adult